The research described in this module will investigate the prognosis and pathologic characteristics of breast cancers occurring in women who have germline mutations in BRCA1 and BRCA2. Prognostic effects will be examined by obtaining clinical, treatment and follow-up information on women who are members of incident cohorts recruited at the three CFRBCS population-based sites (Ontario, Australia, Northern California); pathologic characteristics will be investigated in women recruited at these sites, as well as those recruited at the three clinic-based sites (Utah, Philadelphia, New York). Our objectives are to compare the risk of breast cancer recurrence and death in women with hereditary breast cancer to those with sporadic breast cancer before and after consideration of treatment and traditional prognostic factors, to investigate the impact of family history on breast cancer outcomes and to characterize the pathology of BRCA1 and BRCA2 associated breast cancer. The impact on distant recurrence of a germline mutation in each gene separately is our primary objective. We will enroll approximately 5910 women; 323 of these are expected to have mutations in BRCA1 and 194 in BRCA2. Clinical, pathology and follow- up data collection will be standardized across center. With a mean follow- up of 6 years by the end of 2003, we will have over 95% powers to detect a 15% increased risk of distant recurrence (our primary study outcome) in women with mutations in BRCA1, and over 90% power to detect this same increased risk in those with mutations in BRCA2. The CFRBCS is in a strong position to carry out this research. The multicenter nature of our group allows us to study large numbers of women in a relatively short period of time. The existence of an established registry provides immediate access to groups of women with hereditary and non-hereditary breast cancer thereby facilitating recruitment, it reduces the burden of data collection and it provides access to results of mutation analysis. Furthermore, the collaborative relationships developed during establishment of the CFRBCS have facilitated agreement about research methodology and data collection for this module. This has led to a timely and cost-effective approach to our current research goals. It also puts in a strong position to examine prognostic discovered genes in the future.